Fri Dec 31 2021

61 articles - From Saturday Dec 25 2021 to Friday Dec 31 2021

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Guidelines

Guidelines, position statements, white papers, technical reviews, consensus statements, etc…

Ann Oncol

Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA).

We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for haematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.

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Meta-analysis

meta-analyses and systematic reviews


Studies

RCT, clinical trials, retrospective studies, etc…

Am J Hematol

Increased blood viscosity and red blood cell aggregation in patients with COVID-19.

RBC aggregation correlated positively with clot firmness, negatively with clot formation time, and positively with the length of hospitalization. Patients with oxygen supplementation had higher RBC aggregation and blood viscosity than those without, and patients with pulmonary lesions had higher RBC aggregation and enhanced coagulation than those without. This study is the first to demonstrate blood hyper-viscosity and RBC hyper-aggregation in a large cohort of patients with COVID-19 and describe associations with enhanced coagulation and clinical outcomes.

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Ann Oncol

COVID-19 vaccination and breakthrough infections in patients with cancer.

Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

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Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis.

With additional follow-up, the tucatinib combination provided a clinically meaningful survival benefit for patients with HER2+ metastatic breast cancer.

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Blood

Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation for B-lineage Acute Lymphoblastic Leukemia.

Responders had higher proportions of effector memory CD8 T-cell subsets. Non-responders were T-cell deficient and expressed more inhibitory checkpoint molecules, including TIM3. We found that blinatumomab post-allogeneic HCT is feasible, and its benefit is dependent on the immune milieu at time of treatment.

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Critical Role of Lama4 for Hematopoiesis Regeneration and Acute Myeloid Leukemia Progression.

Notably, LAMA4 inhibition or knockdown in human MSCs promoted human AML cell proliferation and chemoprotection. Together, our study for the first time demonstrates a critical role of Lama4 in impeding AML progression and chemoresistance. Targeting Lama4 signaling pathways may offer potential new therapeutic options for AML.

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Molecular and cellular mechanisms that regulate human erythropoiesis.

We additionally discuss the insights gained by studying human genetic variation impacting erythropoiesis and highlight the discovery of BCL11A as a regulator of hemoglobin switching through genetic studies. Finally, we provide an outlook of how our ability to measure multiple facets of this process at single-cell resolution, while accounting for the impact of human variation, will continue to refine our knowledge of erythropoiesis and how this process is perturbed in disease. As we learn more about this intricate and important process, additional opportunities to modulate erythropoiesis for therapeutic purposes will undoubtedly emerge.

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Obinutuzumab plus lenalidomide (GALEN) in advanced, previously untreated follicular lymphoma in need of systemic therapy.

Except for neutropenia, the safety profile of the combination is remarkable. The study was registered with ClinicalTrials. gov, number NCT01582776.

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Overcoming IMiD Resistance in T-cell Lymphomas Through Potent Degradation of ZFP91 and IKZF1.

By activating keynote genes from WNT, NF-kB, and MAP kinase signaling, ZFP91 directly promotes resistance to IKZF1 loss. Moreover, lenalidomide-sensitive TCLs can acquire stable resistance via ZFP91 rewiring, which involves casein kinase 2 (CK2) mediated c-Jun inactivation. Overall, these findings identify a critical transcription factor network within TCLs and provide clinical proof of concept for the novel therapy using next-generation degraders.

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SOD2 V16A Amplifies Vascular Dysfunction in Sickle Cell Patients by Curtailing Mitochondria Complex IV Activity.

SOD2V16A increases hydrogen peroxide and mitochondrial reactive oxygen species (ROS) production compared to controls. Unexpectedly, the increased ROS was not due to SOD2V16A mislocalization but was associated with mitochondrial Complex IV and a concomitant decrease in basal respiration and Complex IV activity. In sum, SOD2V16A is a novel clinical biomarker of cardiovascular dysfunction in SCD patients through its ability to decrease mitochondrial Complex IV activity and amplify ROS production in the endothelium.

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Suppression of fibrin(ogen)-driven pathologies through controlled knockdown by lipid nanoparticle delivery of siRNA.

In a sterile peritonitis model, siFga restored normal macrophage migration in plasminogen-deficient mice. Finally, treatment of mice with siFga decreased the metastatic potential of tumour cells in a manner comparable to that observed in fibrinogen-deficient mice. The results indicate that siFga causes robust and controllable depletion of fibrinogen and provide the proof-of-concept that this strategy can modulate the pleiotropic effects of fibrinogen in relevant disease models.

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Blood Adv

Checkpoint protein expression in the tumor microenvironment defines the outcome of classical Hodgkin lymphoma patients.

cHLs with high proportions of checkpoint proteins overexpressed genes coding for cytolytic factors, proposing paradoxically that they were immunologically active. This checkpoint molecule gene signature translated to inferior survival in a validation cohort of 290 diagnostic cHL samples (P<0.001) and in an expansion cohort of 84 cHL relapse samples (P=0.048). Our findings demonstrate the impact of T cell- and macrophage-mediated checkpoint system on the survival of patients with cHL.

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COVID-19 vaccination in patients with immune thrombocytopenia.

Risk factors for ITP exacerbation were platelet count <50x109/L (OR 5.3, 95%CI 2.1-13.7), ITP treatment at time of vaccination (OR 3.4, 95%CI 1.5-8.0) and age (OR 0.96 per year, 95%CI 0.94-0.99). Our study highlights safety of COVID-19 vaccination in ITP patients and importance of close monitoring platelet counts in a subgroup of ITP patients. ITP patients with exacerbation responded well on therapy.

Pubmed   Journal   ReadQx   PMC

Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma.

Gene expression analysis of pre-treatment tumor biopsies indicated that tumor cell intrinsic factors like TP53 signaling are associated with resistance to glofitamab, but may also be interlinked with a diminished effector T-cell profile in resistant tumors and thus represent a poor prognostic factor per se. This integrative biomarker data analysis provides clinical evidence of glofitamab's mode of action, supports optimal biological dose selection, and will further guide clinical development.

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Predictors of response and survival in a large cohort of 319 Waldenström macroglobulinemia patients treated with ibrutinib monotherapy.

Age 65 years or older was the only factor associated with overall survival (HR 3.2, 95% CI 1.4-7.0; p=0.005). Multiple imputation analyses did not alter our results. Our study confirms the predictive and prognostic value of CXCR4 mutations in patients with WM treated with ibrutinib monotherapy.

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Sodium stibogluconate and CD47-SIRPa blockade overcome resistance of anti-CD20-opsonized B cells to neutrophil killing.

SSG enhanced neutrophil-mediated ADCC of solid tumor cells, but enabled B lymphoma cell trogoptotic killing, by turning trogocytosis from a resistance-contributing mechanism into a cytotoxic anti-cancer one. The killing in the presence of SSG required both antibody opsonization of the target cells, as well as disruption of CD47-SIRPa interactions. These results provide a more detailed understanding of the role of neutrophil trogocytosis in antibody-mediated destruction of B cells and clues on how to further optimize antibody therapy of B cell malignancies.

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Blood Cancer J

Risk of non-Hodgkin lymphoma in breast cancer survivors: a nationwide cohort study.

The adjusted HR for NHL was much higher in participants who were aged<50years and who received hormone therapy (either tamoxifen or aromatase inhibitors) than in those =50years or who did not receive hormone therapy, respectively. The development of breast cancer was associated with a significantly increased risk of NHL, particularly follicular lymphoma and mature T/NK-cell lymphoma. In particular, the risk of NHL was higher in patients receiving hormone therapy and in younger patients.

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Transformation and outcome of nodular lymphocyte predominant Hodgkin lymphoma: a Finnish Nationwide population-based study.

The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.150.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time.

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Haematologica

Did brentuximab vedotin's rise to the top ECHELON of Hodgkin therapeutics invalidate AETHERA results?

Not available.

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Effect of PAS-C on short-term cold-stored platelets in vitro and in vivo.

Not available.

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Kikuchi-Fujimoto disease associated with hemophagocytic lymphohistiocytosis following the BNT162b2 mRNA COVID-19 vaccination.

Not available.

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Mitochondrial ATP generation in stimulated platelets is essential for granule secretion but dispensable for aggregation and procoagulant activity.

Not available.

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Outcomes of refractory or relapsed Hodgkin lymphoma patients with post autologous stem cell transplantation brentuximab vedotin maintenance : a French multicenter observational cohort study.

Not available.

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Phase 1b dose-escalation study of the selective, noncovalent, reversible Bruton's tyrosine kinase inhibitor vecabrutinib in B-cell malignancies.

Not available.

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Platelet-activating anti-PF4 antibodies mimicking VITT antibodies in an unvaccinated patient with monoclonal gammopathy.

Not available.

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Rational drug combinations with CDK4/6 inhibitors in acute lymphoblastic Leukemia.

Importantly, simultaneous but not sequential treatment of CDKis with conventional chemotherapy (dexamethasone, L-asparaginase and vincristine) led to improved efficacy compared to monotherapy in vivo. We provide novel evidence that combining CDKis and conventional chemotherapy can be safe and effective. These results led to the rational design of a clinical trial.

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Zanubrutinib, rituximab and lenalidomide induces deep and durable remission in TP53 mutated B-cell prolymphocytic leukemia: a case report and review of literature.

Not available.

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Thromb Haemost

Do Patients with a Family or Personal History of Venous Thromboembolism have an Increased Risk of Recurrence?

Our findings indicate that in patients with acute VTE, a FH and/or PH of VTE does not convey an increased risk of recurrent VTE. In particular, we did not find a "dose-effect" relationship between FH/PH status and VTE recurrence.

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Effectiveness and Safety of Apixaban versus Warfarin in Venous Thromboembolism Patients with Chronic Kidney Disease.

When stratified by CKD stage (stage I/II: 8.2%; stage III: 49.4%; stage IV: 12.8%; stage V/ESRD: 12.0%; stage unspecified: 17.6%), no significant interaction was observed for effects of apixaban versus warfarin on recurrent VTE or MB. In summary, apixaban was associated with a significantly lower risk of recurrent VTE and MB than warfarin among VTE patients with CKD. CKD stages did not have significant impact on treatment effects for recurrent VTE and MB.

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Reviews&Editorials

Plenty of the editorials are available as full text through the publisher website using the provided link

Ann Oncol

Should Ki-67 be adopted to select breast cancer patients for treatment with adjuvant abemaciclib?

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Blood

A CMV seronegative donor to avoid T-cell inflation?

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Can we do something about ICH in hemophilia?

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Diagnosed with myeloma before age 40.

Pubmed   Journal   ReadQx   PMC

HLA in AA: innocent bystander or culprit?

Pubmed   Journal   ReadQx 

Is this a cure for XMEN?

Pubmed   Journal   ReadQx 

JAK/STAT: a pathway through the maze of PTCL?

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MRD in CLL: some answers, many questions.

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NPM1: not present? Mark!

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Old drug revisited: disulfiram, NETs, and sepsis.

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Prime suspects: cross-presenting platelet EVs.

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Ticket to divide: m6A reader YTHDC1 drives acute myeloid leukemia proliferation.

Pubmed   Journal   ReadQx   PMC

TP53 mutations in CLL: does frequency matter?

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Turning AML targets inside out.

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Two-hit strategy for treating AL amyloidosis?

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Understanding CLL biology through mouse models of human genetics.

In this review, we describe the application of mouse models to the studies of CLL pathogenesis and disease transformation from an indolent to a high-grade malignancy (ie, Richter syndrome [RS]) and treatment, with a focus on newly developed genetically inspired mouse lines modeling recurrent CLL genetic events. We discuss how these novel mouse models, analyzed using new genomic technologies, allow the dissection of mechanisms of disease evolution and response to therapy with greater depth than previously possible and provide important insight into human CLL and RS pathogenesis and therapeutic vulnerabilities. These models thereby provide valuable platforms for functional genomic analyses and treatment studies.

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CA Cancer J Clin

An overview of real-world data sources for oncology and considerations for research.

Careful consideration of each data type is necessary because they are collected for a specific purpose, capturing a set of data elements within a certain population for that purpose, and they vary by population coverage and longitudinality. In this review, the authors provide a high-level assessment of the strengths and limitations of each data category to inform data source selection appropriate to the study question. Overall, the development and accessibility of RWD sources for cancer research are rapidly increasing, and the use of these data requires careful consideration of composition and utility to assess important questions in understanding the use and effectiveness of new therapies.

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Letters&Replies

Letters to the editors and authors’ replies

Am J Hematol

Landscape and clinical significance of long noncoding RNAs involved in multiple myeloma expressed fusion transcripts.

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Lymphocytopenia predicts shortened survival in myelodysplastic syndrome with ring sideroblasts (MDS-RS) but not in MDS/MPN-RS-T.

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The clinical course and life expectancy of patients with multiple myeloma who discontinue their first daratumumab-containing line of therapy.

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Voxelotor use in adults with sickle cell disease in a real-world setting.

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Ann Oncol

Too much for some and too little for others.

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Blood Adv

Impaired immune response to COVID-19 vaccination in patients with B-cell malignancies after CD19 CAR T-cell therapy.

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Others

all remaining publications eg case reports, images of the month, etc…

Blood

Atypical CML with mutated SRSF2, ASXL1, CSF3R, and MPL.

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EBV+ ALK+ large B-cell lymphoma.

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HLA alleles, mutations, and outcomes in immune AA.

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Platelet clump visible to the naked eye in type 2B von Willebrand disease.

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Blood Adv

Is BTKi or BCL2i preferable as first novel therapy in patients with CLL? The case for BCL2i.

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Is BTKi or BCL2i preferable as first novel therapy in patients with CLL? The Case for BTKi.

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Lancet Haematol

2021 ASH annual meeting.

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Leukemia

SARS-CoV-2 specific cellular response following COVID-19 vaccination in patients with chronic lymphocytic leukemia.

Pubmed   Journal   ReadQx   PMC

Thromb Haemost

Gene Abnormalities in Transplant Associated-Thrombotic Microangiopathy: Comparison between Recipient and Donor's DNA.

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